Neutralization of Interleukin‐17 Attenuates Cholestatic Liver Fibrosis in Mice
Open accessAbstract
Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. IL‐17 is critical in inflammation, but the role of IL‐17 in liver fibrosis has not yet been elucidated. In this study, we investigate the role of IL‐17 on bile duct ligation‐induced liver injury and fibrosis in C57BL/6 mice. Animals were sacrificed at designated times, and serum and liver tissues were collected for analysis of liver function and serum IL‐6, IL‐1β, tumour necrosis factor‐alpha (TNF‐α) and transforming growth factor‐β (TGF‐β) levels. IL‐17 blockade with anti‐IL‐17A mAb significantly improved liver function and decreased hepatocellular necrosis, pro‐inflammatory cytokines, neutrophils and macrophages influx. Furthermore, CD3 + and CD8 + lymphocytes, neutrophils and macrophages were found to express IL‐17, and neutrophils are the principal IL‐17‐producing cells after BDL‐induced liver injury. These data indicated that IL‐17 signal contributes to the pathogenesis of cholestatic liver injury and blocked of IL‐17 could potentially benefit patients with cholestatic liver disease.
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Stimulation of TLR4/NFkB in hepatic stellate cells enhances TGF-β signaling by downregulating the TGF-β pseudoreceptor Bambi.
“stimulation of TLR4/NFkB in hepatic stellate cells enhances TGF-β signaling by directly downregulating the TGF-β pseudoreceptor BMP and the activin membrane-bound inhibitor Bambi127”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [127]
Hepatic stellate cells express all known human TLRs and respond to TLR4 ligands, which also downregulate a TGF-β1 decoy receptor sensitizing HSC to TGF-β1.
“HSCs express all known human TLRs and respond to TLR4 ligands127,163, which also downregulate a TGF-β1 decoy receptor sensitizing HSC to the action of TGF-β1127”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [127]
Blocking TLR4 signaling in mice or reducing hepatic exposure to intestinal microbes by reducing microbial load with antibiotics ameliorates experimental liver fibrosis.
“Blocking TLR4 signaling in mice or reducing hepatic exposure to intestinal microbes by reducing microbial load with antibiotics ameliorates experimental liver fibrosis127”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [127]
TLR4 was protective in the lung, as opposed to its pathogenic effect in gut and liver fibrosis.
“Interestingly, TLR4 was protective in the lung, as opposed to its pathogenic effect in gut and liver fibrosis127,159”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [127]
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Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868 · see citing works
- Authors
- Zhang, S., Huang, D., Weng, J., Huang, Y., Liu, S., Zhang, Q., Li, N., Wen, M., Zhu, G., Lin, F., & Gu, W.
- Affiliations
- Guangzhou First People's Hospital (CN)
- Corresponding author
- Gu, W.
- Venue
- Scandinavian Journal of Immunology
- Publisher
- Wiley
- Published
- 2016-01-28
- Volume
- 83
- Issue
- 2
- Pages
- 102-108
- ISSN
- 0300-9475 (ISSN-L)
- 1365-3083
- OpenAlex
- W1814471289
- Cited by
- 36
- References
- 30
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 2
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Scandinavian Journal of Immunology (publishedVersion, cc-by-nd)
- PubMed (publishedVersion)
- Funders
- Guangdong province (2013B021800057)
- Projects of medical and health technology development program in Guangzhou -general guide project (20131A011029, 20141A010003)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- IL-17, cholestatic liver fibrosis, bile duct ligation, anti-IL-17A monoclonal antibody, liver necrosis, neutrophils, macrophages, inflammatory cytokines, liver inflammation, cholestatic liver injury, T cell infiltration
- MeSH terms
- Animals, Antibodies, Monoclonal, Bile Ducts, Cholestasis, Disease Models, Animal, Humans, Ligation, Liver Cirrhosis, Male, Mice, Inbred C57BL, Molecular Sequence Data, Neutrophils, RNA, Messenger, Cytokines, Inflammation Mediators, Interleukin-17, Mice, Antibodies, Neutralizing
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